Measuring concentrations of administered drugs and their metabolites in biological fluids, such as whole blood, plasma and serum, is important to understanding the efficacy and toxicological effects of the drugs. Typical clinical studies require handling and processing large numbers of biological fluid samples at low temperature with special care. Dried spot sampling is an alternative to the current practice and is based on collection of small volumes (e.g., several microliters or less) of biological fluids as dried spots. For example, dried blood spot (DBS) sampling involves the collection of small volumes of blood on a carrier medium. The reduced sample size and the convenience of compact carrier mediums results in easier sample handling and reduced shipping costs. Samples are reconstituted from the dried spots using suitable solvents during an extraction process. The reconstituted samples can be analyzed, for example, in a liquid chromatography-mass spectrometry (LC-MS) assay.
In many instances, the above technique fails to deliver a desirable detection sensitivity and ease of use. The dried spots can vary in analyte concentration due, for example, to the hematocrit of the subject. To improve repeatability, sampling of the entire dried spot is generally required. Conventional techniques include punching the dried spots from sample cards. Typical punching processes use a sharp punch tool. Repeated use of the punch tool can lead to carryover. Moreover, the process of punching the spots is tedious for the clinician and can be a limiting step in the overall work flow.